Higher Cerebral Blood Flow Research Articles

Quantitative association of cerebral blood flow, relaxation times and proton density in young and middle-aged primary insomnia patients: A prospective study using three-dimensional arterial spin labeling and synthetic magnetic resonance imaging.

To quantitatively measure the T1 value, T2 value, proton density (PD) value, and cerebral blood flow (CBF) in young and middle-aged primary insomnia (PI) patients, and analyze the correlations between relaxation times, PD, and CBF to explore potential brain changes. Cranial magnetic resonance (MR) images of 44 PI patients and 30 healthy subjects were prospectively collected for analysis. The T1, T2, PD, and CBF values of the frontal lobe, parietal lobe, temporal lobe, and occipital lobe were independently measured using three-dimensional arterial spin labeling (3D-ASL), synthetic magnetic resonance imaging (syMRI) and a whole-brain automatic segmentation method. The differences of these imaging indices were compared between PI patients and healthy subjects. Follow-up MR images were obtained from PI patients after 6 months to compare with pre-treatment images. The Wilcoxon signed rank test and Spearman rank were used for statistical analysis. Bilateral CBF asymmetry was observed in 38 patients, with significant differences in both the T2 value and CBF between the four lobes of the brain (p < 0.01). However, no significant difference was found in the T1 and PD values between the bilateral lobes. A negative correlation was found between CBF and T2 values in the right four lobes of patients with primary insomnia (PI). During follow-up examinations, five PI patients showed a disappearance of insomnia symptoms and a decrease in CBF in both brain lobes. Insomnia symptoms may be associated with high CBF, and most PI patients have higher CBF and lower T2 values in the right cerebral hemispheres. The right hemisphere appears to play a critical role in the pathophysiology of PI. The 3D-ASL and syMRI technologies can provide a quantitative imaging basis for investigating the brain conditions and changes in young and middle-aged PI patients.

Dynamic 3D imaging of cerebral blood flow in awake mice using self-supervised-learning-enhanced optical coherence Doppler tomography

Cerebral blood flow (CBF) is widely used to assess brain function. However, most preclinical CBF studies have been performed under anesthesia, which confounds findings. High spatiotemporal-resolution CBF imaging of awake animals is challenging due to motion artifacts and background noise, particularly for Doppler-based flow imaging. Here, we report ultrahigh-resolution optical coherence Doppler tomography (µODT) for 3D imaging of CBF velocity (CBFv) dynamics in awake mice by developing self-supervised deep-learning for effective image denoising and motion-artifact removal. We compare cortical CBFv in awake vs. anesthetized mice and their dynamic responses in arteriolar, venular and capillary networks to acute cocaine (1 mg/kg, i.v.), a highly addictive drug associated with neurovascular toxicity. Compared with awake, isoflurane (2-2.5%) induces vasodilation and increases CBFv within 2-4 min, whereas dexmedetomidine (0.025 mg/kg, i.p.) does not change vessel diameters nor flow. Acute cocaine decreases CBFv to the same extent in dexmedetomidine and awake states, whereas decreases are larger under isoflurane, suggesting that isoflurane-induced vasodilation might have facilitated detection of cocaine-induced vasoconstriction. Awake mice after chronic cocaine show severe vasoconstriction, CBFv decreases and vascular adaptations with extended diving arteriolar/venular vessels that prioritize blood supply to deeper cortical capillaries. The 3D imaging platform we present provides a powerful tool to study dynamic changes in vessel diameters and morphology alongside CBFv networks in the brain of awake animals that can advance our understanding of the effects of drugs and disease conditions (ischemia, tumors, wound healing).

Greater accelerometer-measured physical activity is associated with better cognition and cerebrovascular health in older adults.

Physical activity (PA) may help maintain brain structure and function in aging. Since the intensity of PA needed to effect cognition and cerebrovascular health remains unknown, we examined associations between PA and cognition, regional white matter hyperintensities (WMH), and regional cerebral blood flow (CBF) in older adults. Forty-three older adults without cognitive impairment underwent magnetic resonance imaging (MRI) and comprehensive neuropsychological assessment. Waist-worn accelerometers objectively measured PA for approximately one week. Higher time spent in moderate to vigorous PA (MVPA) was uniquely associated with better memory and executive functioning after adjusting for all light PA. Higher MVPA was also uniquely associated with lower frontal WMH volume although the finding was no longer significant after additionally adjusting for age and accelerometer wear time. MVPA was not associated with CBF. Higher time spent in all light PA was uniquely associated with higher CBF but not with cognitive performance or WMH volume. Engaging in PA may be beneficial for cerebrovascular health, and MVPA in particular may help preserve memory and executive function in otherwise cognitively healthy older adults. There may be differential effects of engaging in lighter PA and MVPA on MRI markers of cerebrovascular health although this needs to be confirmed in future studies with larger samples. Future randomized controlled trials that increase PA are needed to elucidate cause-effect associations between PA and cerebrovascular health.

Cerebral Perfusion and Cortical Thickness Predict Cognitive Impairment in a Community‐dwelling Cohort

AbstractBackgroundNeurodegeneration and cerebral perfusion are key neuroimaging biomarkers in the Alzheimer’s Disease continuum. ASL (arterial spin labeling) explores cerebral blood flow (CBF) and has aided in elucidating cerebrovascular health amongst people at risk of cognitive decline. Reduced cortical thickness (CT) on MRI is a neurodegeneration biomarker that also implicated in cognitive impairment. The influence of cortical thickness and perfusion in AD‐related regions on cognitive status is poorly understood. We explored markers to investigate the roles they had in cognitive impairment.MethodParticipants enrolled in the Wake Forest Alzheimer’s Disease Research Center (ADRC) Clinical Core cohort (N= 535, Table 1) underwent baseline T1/ASL MRI. Participants were adjudicated as cognitively impaired (CI: mild cognitive impairment or AD) or cognitively unimpaired (CU) using NIA‐AA criteria by a consensus panel of experts. CT in an AD‐related temporal lobe meta‐ROI (region of interest) was calculated on T1 using FreeSurfer v5.3 and standardized. A homologous set of AD‐sensitive temporal lobe ROIs was used to extract mean CBF, which was log transformed for normality. A one‐way MANOVA (covariates: age, education, sex) assessed effects of CT and CBF on cognitive impairment. Bivariate models evaluated the associations of CT and CBF in relation to age, education, sex, and cognitive impairment. Linear regression was used to analyze whether cognitive impairment was predicted by CT and CBF (adjusted).ResultWe found both CBF and CT were associated with age (r2= ‐0.142, p&lt;0.01; r2= ‐0.339; p&lt;0.01) and cognitive status (r2= ‐0.188, p&lt;0.01; r2= ‐0.264; p&lt;0.01); respectively. CBF was also associated with sex (r2= 0.083; p=0.055) such that women had higher CBF. We also found that higher CBF was marginally associated with higher CT (r2= 0.083; p=0.055); this relationship was not significant when age, sex, and education were included in the model (r2= 0.886; p=0.376). Finally, we found both CT and CBF predicted cognitive impairment (p&lt;0.01; both unadjusted and adjusted, in models where each MRI marker was used to predict cognition), such that CBF and CT were higher in CU; further, both CBF and CT independently predicted cognitive status when together in a model (p&lt;0.008).ConclusionCortical thickness and CBF are predictive of cognitive impairment.

CTNI-61. CLINICAL EFFICACY AND PREDICTIVE BIOMARKERS OF ONC201 IN H3K27M-MUTANT DIFFUSE MIDLINE GLIOMA

Abstract Patients with H3K27M-mutated diffuse midline glioma (DMG) have no proven effective therapies beyond radiation. ONC201, a DRD2 antagonist and mitochondrial ClpP agonist, has shown promise in this population. Clinical and genetic variables associated with ONC201 response in H3K27M-mutant DMG continue to be investigated. A combined clinical and genetic study evaluated patients with H3K27M-DMG treated with single-agent ONC201 at the established phase 2 dose. Clinical outcomes of patients treated on two recently completed multi-site clinical studies (NCT03416530 and NCT03134131, n = 75) were compared with historical control data from patients with confirmed H3K27M-DMG (n = 391 total, n = 119 recurrent). Patients treated with ONC201 monotherapy following initial radiation, but prior to recurrence, demonstrated a median overall survival (OS) of 25.6 months from diagnosis and recurrent patients demonstrated a median OS of 16.2 months from recurrence, both of these more than doubling historical outcomes. Using a Cox model to correct for age, gender and tumor location, OS of ONC201-treated patients with H3K27M-mutant tumors remained significantly better than non-ONC201-treated historical controls (p = 0.0001). A survival and radiographic analysis based on tumor location, revealed stronger responses in thalamic patients. In patients with thalamic tumors treated after initial radiation (n = 16), median OS was not reached with median follow up of 22.1 months (historical control median OS of 12.5 months, n = 83, p = 0.0001). Significant correlations were found between baseline cerebral blood flow (CBF) on perfusion imaging and OS (Pearson’s r = 0.75, p = 0.003) and between nrCBF and PFS (r = 0.77, p = 0.002). Baseline tumor sequencing from treated patients (n = 20) demonstrates EGFR mutation (n = 3) and high EGFR expression as a marker of resistance and improved response in tumors with MAPK-pathway alterations (n = 5). In conclusion, ONC201 demonstrates unprecedented clinical and radiographic efficacy in H3K27M-mutant DMG with outcomes enriched in patients with thalamic tumors, treatment prior to recurrence, MAPK-pathway alterations, and patients with relatively high CBF.

Altered Cerebral Blood Flow is Linked to Disease Duration in Patients with Generalized tonic‒clonic Seizures

To investigate cerebral blood flow (CBF) characteristics in individuals with generalized tonic‒clonic seizures (GTCS) during theinterictalphase using voxel-based analysis of 3D pseudocontinuous arterial spin labeling (PCASL). Patients with GTCS (GTCS group) (during the interictal period) and healthy volunteers (control group) underwent head MR imaging with a 3.0T MR scanner with a 3D PCASL sequence. CBF was compared between the two groups. Spearman correlations of CBF in regions of interest (ROIs) in GTCS patients with the duration of disease and age of onset were analyzed and corrected using the false discovery rate (FDR). Twenty patients with GTCS (GTCS group) and twenty healthy volunteers (control group) were recruited for this study. On 3D PCASL, (1) GTCS patients had lower CBF in the brainstem, right cerebellum, right inferior temporal gyrus, parahippocampal gyrus, superior frontal gyrus, middle frontal gyrus, triangular part of inferior frontal gyrus, left temporal pole of superior temporal gyrus and thalamus and had higher CBF in the bilateral superior parietal gyri, precuneus, precentral gyri, postcentral gyri, and left dorsolateral superior frontal gyrus than controls. (2) The CBF of the right temporal pole of the middle temporal gyrus was negatively correlated with the duration of disease (PFDRcorrected<0.05), with a correlation coefficient r of -0.7333 and a PFDRcorrected value of 0.04. Voxel-based analysis of3D PCASL imaging can be used to sensitively detect brain perfusion differences in GTCS patients. The decrease in CBF in the right temporal pole of the middle temporal gyrus may be associated with disease onset. These findings may offer new perspectives on the pathogenesis of GTCS and the underlying pathophysiological changes associated with perfusion.

Intense long-term training impairs brain health compared with moderate exercise: Experimental evidence and mechanisms.

The consequences of extremely intense long-term exercise for brain health remain unknown. We studied the effects of strenuous exercise on brain structure and function, its dose-response relationship, and mechanisms in a rat model of endurance training. Five-week-old male Wistar rats were assigned to moderate (MOD) or intense (INT) exercise or a sedentary (SED) group for 16 weeks. MOD rats showed the highest motivation and learning capacity in operant conditioning experiments; SED and INT presented similar results. In vivo MRI demonstrated enhanced global and regional connectivity efficiency and clustering as well as a higher cerebral blood flow (CBF) in MOD but not INT rats compared with SED. In the cortex, downregulation of oxidative phosphorylation complex IV and AMPK activation denoted mitochondrial dysfunction in INT rats. An imbalance in cortical antioxidant capacity was found between MOD and INT rats. The MOD group showed the lowest hippocampal brain-derived neurotrophic factor levels. The mRNA and protein levels of inflammatory markers were similar in all groups. In conclusion, strenuous long-term exercise yields a lesser improvement in learning ability than moderate exercise. Blunting of MOD-induced improvements in CBF and connectivity efficiency, accompanied by impaired mitochondrial energetics and, possibly, transient local oxidative stress, may underlie the findings in intensively trained rats.

Estimation of Cerebral Blood Flow and Arterial Transit Time From Multi-Delay Arterial Spin Labeling MRI Using a Simulation-Based Supervised Deep Neural Network.

An inherently poor signal-to-noise ratio (SNR) causes inaccuracy and less precision in cerebral blood flow (CBF) and arterial transit time (ATT) when using arterial spin labeling (ASL). Deep neural network (DNN)-based parameter estimation can solve these problems. To reduce the effects of Rician noise on ASL parameter estimation and compute unbiased CBF and ATT using simulation-based supervised DNNs. Retrospective. One million simulation test data points, 17 healthy volunteers (five women and 12 men, 33.2 ± 14.6 years of age), and one patient with moyamoya disease. 3.0 T/Hadamard-encoded pseudo-continuous ASL with a three-dimensional fast spin-echo stack of spirals. Performances of DNN and conventional methods were compared. For test data, the normalized mean absolute error (NMAE) and normalized root mean squared error (NRMSE) between the ground truth and predicted values were evaluated. For in vivo data, baseline CBF and ATT and their relative changes with respect to SNR using artificial noise-added images were assessed. One-way analysis of variance with post-hoc Tukey's multiple comparison test, paired t-test, and the Bland-Altman graphical analysis. Statistical significance was defined as P < 0.05. For both CBF and ATT, NMAE and NRMSE were lower with DNN than with the conventional method. The baseline values were significantly smaller with DNN than with the conventional method (CBF in gray matter, 66 ± 10 vs. 71 ± 12 mL/100 g/min; white matter, 45 ± 6 vs. 46 ± 7mL/100 g/min; ATT in gray matter, 1424 ± 201 vs. 1471 ± 154 msec). CBF and ATT increased with decreasing SNR; however, their change rates were smaller with DNN than were those with the conventional method. Higher CBF in the prolonged ATT region and clearer contrast in ATT were identified by DNN in a clinical case. DNN outperformed the conventional method in terms of accuracy, precision, and noise immunity. 3 Technical Efficacy: Stage 1.

Effects of bolus injection duration on perfusion estimates in dynamic CT and dynamic susceptibility contrast MRI

Estimates of cerebral blood flow (CBF) and tissue mean transit time (MTT) have been shown to differ between dynamic CT perfusion (CTP) and dynamic susceptibility contrast MRI (DSC-MRI). This study investigates whether these discrepancies regarding CBF and MTT between CTP and DSC-MRI can be attributed to the different injection durations of these techniques. Five subjects were scanned using CTP and DSC-MRI. Region-wise estimates of CBF, MTT, and cerebral blood volume (CBV) were derived based on oscillatory index regularized singular value decomposition. A parametric model that reproduced the shape of measured time curves and characteristics of resulting perfusion parameter estimates was developed and used to simulate data with injection durations typical for CTP and DSC-MRI for a clinically relevant set of perfusion scenarios and noise levels. In simulations, estimates of CBF/MTT showed larger negative/positive bias and increasing variability for CTP when compared to DSC-MRI, especially for high CBF levels. While noise also affected estimates, at clinically relevant levels, the injection duration effect was larger. There are several methodological differences between CTP and DSC-MRI. The results of this study suggest that the injection duration is among those that can explain differences in estimates of CBF and MTT between these bolus tracking techniques.

Cerebral blood flow is associated with markers of neurodegeneration in Huntington’s disease

IntroductionThe ultimate cause of neuronal death in Huntington's disease (HD) is still uncertain. Apart from impairment in systems handling abnormal proteins, other mechanisms might contribute to neurodegeneration and progression of HD. Decreased cerebral blood flow (CBF) has been described in other neurodegenerative disorders and may play a role in HD. ObjectivesTo investigate CBF changes in HD gene carriers. MethodsA group of 39 HD gene carriers (18 premanifest and 21 manifest HD) and 16 controls underwent a comprehensive clinical evaluation and a brain magnetic resonance imaging protocol that included pseudo-continuous arterial spin labeling to quantify CBF. Regions of interest (ROI) analyses were performed to compare CBF in controls vs premanifest HD vs manifest HD. Correlation analyses were performed to ascertain the relationship between CBF and clinical and biomarkers data. ResultsWe found a decrease in CBF in bilateral caudate and putamen of patients with manifest HD in comparison with controls. CBF of premanifest HD carriers in the same ROIs was midway between controls and the HD patients, with differences not reaching statistical significance. Lower CBF in caudate and putamen was associated with worse motor symptoms, functionality, and cognitive performance. CBF was also associated with markers of neurodegeneration: higher CBF in caudate and putamen significantly correlated to higher volumes in the same ROI and to lower levels of neurofilament light chain. ConclusionAs CBF changes in caudate and putamen nuclei were associated with markers of neurodegeneration and with clinical outcomes, decreased CBF and oxygen supply could emerge as a relevant mechanism contributing to degeneration in HD.

The characteristics of arterial spin labeling cerebral blood flow in patients with subjective cognitive decline: The Chinese imaging, biomarkers, and lifestyle study.

ObjectiveWe aimed to characterize the potential risk factors and cerebral perfusion of patients with subjective cognitive decline (SCD).MethodsThis prospective study enrolled consecutive patients from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) Cohort of Alzheimer’s disease between February 2021 and March 2022. Patients who met the SCD diagnostic criteria were categorized into the SCD group, while those without cognitive complaints or any concerns were assigned to the healthy control (HC) group. The demographic and clinical characteristics and cerebral blood flow (CBF) from pseudo-continuous arterial spin labeling (pCASL) in standard cognitive regions were compared between these two groups. A multivariate analysis was performed to identify independent factors associated with SCD.ResultsThe frequency of family history of dementia in the SCD group was higher compared with the HC group (p = 0.016). The CBF of left hippocampus (p = 0.023), left parahippocampal gyrus (p = 0.004), left precuneus (p = 0.029), left middle temporal gyrus (p = 0.022), right parahippocampal gyrus (p = 0.018), and right precuneus (p = 0.024) in the SCD group were significantly increased than those in the HC group. The multivariate logistic regression analyses demonstrated that the family history of dementia [OR = 4.284 (1.096–16.747), p = 0.036] and the CBF of left parahippocampal gyrus [OR = 1.361 (1.006–1.840), p = 0.045] were independently associated with SCD.ConclusionThis study demonstrated that the family history of dementia and the higher CBF within the left parahippocampal gyrus were independent risk factors associated with patients with SCD, which could help in the early identification of the SCD and in intervening during this optimal period.

Cerebral blood flow network differences correlated with cognitive impairment in mild traumatic brain injury.

PurposeTo examine whether the cerebral blood flow (CBF) and CBF connectivity differences are sex-specific and whether these differences are correlated with cognitive impairment in mTBI.MethodsResting-state perfusion magnetic resonance imaging was performed in 40 patients with acute mTBI and 40 healthy controls by using pseudocontinuous arterial spin labeling within 14 days following injury. The differences in normalized CBF were first compared and CBF connectivity of the brain regions with significant CBF differences were compared next. The association between the normalized CBF and CBF connectivity differences and cognitive function were further investigated.ResultsMen patients had lower normalized CBF in the frontal gyrus, temporal gyrus and hippocampus and decreased negative CBF connectivity between brain regions including the hippocampus, temporal gyrus, postcentral gyrus and lenticular nucleus, putamen, compared with men controls. Women patients had lower normalized CBF in the frontal gyrus, however had higher normalized CBF in the temporal gyrus and hippocampus, compared with women controls. Additionally, women patients showed increased positive CBF connectivity between the seed region of interest (ROI) of the right inferior temporal gyrus and temporal gyrus and frontal gyrus, and had increased positive CBF connectivity between the seed ROI of the right hippocampus and the temporal gyrus. Furthermore, men patients had higher CBF in the right middle temporal gyrus and left precentral gyrus than women patients.ConclusionThis study provides evidence of sex differences in both decreased and increased CBF and CBF connectivity and association with cognitive outcome in the acute stage after mTBI.

Higher intracranial pressure variability is associated with lower cerebrovascular resistance in aneurysmal subarachnoid hemorrhage

Higher intracranial pressure variability (ICPV) has been associated with a more favorable cerebral energy metabolism, lower rate of delayed ischemic neurologic deficits, and more favorable outcome in aneurysmal subarachnoid hemorrhage (aSAH). We have hypothesized that higher ICPV partly reflects more compliant and active cerebral vessels. In this study, the aim was to further test this by investigating if higher ICPV was associated with lower cerebrovascular resistance (CVR) and higher cerebral blood flow (CBF) after aSAH. In this observational study, 147 aSAH patients were included, all of whom had been treated in the Neurointensive Care (NIC) Unit, Uppsala, Sweden, 2012–2020. They were required to have had ICP monitoring and at least one xenon-enhanced computed tomography (Xe-CT) scan to study cortical CBF within the first 2 weeks post-ictus. CVR was defined as the cerebral perfusion pressure in association with the Xe-CT scan divided by the concurrent CBF. ICPV was defined over three intervals: subminute (ICPV-1m), 30-min (ICPV-30m), and 4 h (ICPV-4h). The first 14 days were divided into early (days 1–3) and vasospasm phase (days 4–14). In the vasospasm phase, but not in the early phase, higher ICPV-4h (β = − 0.19, p < 0.05) was independently associated with a lower CVR in a multiple linear regression analysis and with a higher global cortical CBF (r = 0.19, p < 0.05) in a univariate analysis. ICPV-1m and ICPV-30m were not associated with CVR or CBF in any phase. This study corroborates the hypothesis that higher ICPV, at least in the 4-h interval, is favorable and may reflect more compliant and possibly more active cerebral vessels.

Individual Watershed Areas in Sickle Cell Anemia: An Arterial Spin Labeling Study.

Previous studies have pointed to a role for regional cerebral hemodynamic stress in neurological complications in patients with sickle cell anemia (SCA), with watershed regions identified as particularly at risk of ischemic tissue injury. Using single- and multi-inflow time (TI) arterial spin labeling sequences (ASL) in 94 patients with SCA and 42 controls, the present study sought to investigate cerebral blood flow (CBF) and bolus arrival times (BAT) across gray matter, white matter with early arrival times, and in individual watershed areas (iWSAs). In iWSAs, associations between hemodynamic parameters, lesion burden, white matter integrity, and general cognitive performance were also explored. In patients, increases in CBF and reductions in BAT were observed in association with reduced arterial oxygen content across gray matter and white matter with early arrival times using both sequences (all p < 0.001, d = −1.55–−2.21). Across iWSAs, there was a discrepancy between sequences, with estimates based on the single-TI sequence indicating higher CBF in association with reduced arterial oxygen content in SCA patients, and estimates based on the multi-TI sequence indicating no significant between-group differences or associations with arterial oxygen content. Lesion burden was similar between white matter with early arrival times and iWSAs in both patients and controls, and using both sequences, only trend-level associations between iWSA CBF and iWSA lesion burden were observed in patients. Further, using the multi-TI sequence in patients, increased iWSA CBF was associated with reduced iWSA microstructural tissue integrity and slower processing speed. Taken together, the results highlight the need for researchers to consider BAT when estimating CBF using single-TI sequences. Moreover, the findings demonstrate the feasibility of multi-TI ASL for objective delineation of iWSAs and for detection of regional hemodynamic stress that is associated with reduced microstructural tissue integrity and slower processing speed. This technique may hold promise for future studies and treatment trials.

Slower Respiration Rate Predicts Lower Pain Sensitivity and Greater Supramarginal Gyrus Activation

The subjective experience of pain is driven by multiple physiological and psychological mechanisms supported by a dynamic interplay between low-level afferent input and higher-order cerebral mechanisms. Volitional changes in respiration rate predict changes in pain. However, it is unknown if naturally slower breathing rate is associated with lower pain sensitivity. Further, the brain mechanisms supporting breathing rate during noxious and innocuous stimulation have not been identified. Seventy-four healthy volunteers were administered innocuous (35°C) and noxious heat (Medoc; ten, 12s plateaus of 49°C) to the back of the right calf during pseudocontinuos arterial spin labeling fMRI acquisition (TI = 3 s, TE = 12 ms, TR = 4 s, reps = 66). A visual analogue scale (0 = no pain – 10 = worst pain imaginable) was used to collect pain intensity ratings after each fMRI series. Respiration rate was continuously acquired using a respiratory transducer (Biopac Systems). Linear regression analyses tested the hypothesized relationship between respiration rate and pain sensitivity (SPSS). Standard preprocessing of the functional images included 9 mm spatial smoothing, registration to MNI template and white matter signal regression. A whole-brain analysis examined the between-subjects neural correlates of respiration rate during noxious heat scans (FSL, z>3.1, cluster corrected p<0.05). Slower respiration rate during noxious and innocuous heat predicted lower pain intensity ratings (r = .26, p = 0.03; r = .28, p = .02 respectively). Slower breathing rate was associated with higher cerebral blood flow in the right supramarginal gyrus (SMG) during noxious heat. Individuals that naturally breathed slower during noxious and innocuous stimulation reported lower pain sensitivity. This is supported by stronger activity in the ipsilateral SMG, a region associated with higher somatic-awareness and attention-reorienting towards endogenously-driven stimuli. We propose that individuals that naturally breath slower might engage pain modulatory mechanisms through higher self-awareness.

Cerebral Blood Flow and Oxygen Delivery in Aneurysmal Subarachnoid Hemorrhage: Relation to Neurointensive Care Targets

BackgroundThe primary aim was to determine to what extent continuously monitored neurointensive care unit (neuro-ICU) targets predict cerebral blood flow (CBF) and delivery of oxygen (CDO2) after aneurysmal subarachnoid hemorrhage. The secondary aim was to determine whether CBF and CDO2 were associated with clinical outcome.MethodsIn this observational study, patients with aneurysmal subarachnoid hemorrhage treated at the neuro-ICU in Uppsala, Sweden, from 2012 to 2020 with at least one xenon-enhanced computed tomography (Xe-CT) obtained within the first 14 days post ictus were included. CBF was measured with the Xe-CT and CDO2 was calculated based on CBF and arterial oxygen content. Regional cerebral hypoperfusion was defined as CBF < 20 mL/100 g/min, and poor CDO2 was defined as CDO2 < 3.8 mL O2/100 g/min. Neuro-ICU variables including intracranial pressure (ICP), pressure reactivity index, cerebral perfusion pressure (CPP), optimal CPP, and body temperature were assessed in association with the Xe-CT. The acute phase was divided into early phase (day 1–3) and vasospasm phase (day 4–14).ResultsOf 148 patients, 27 had underwent a Xe-CT only in the early phase, 74 only in the vasospasm phase, and 47 patients in both phases. The patients exhibited cerebral hypoperfusion and poor CDO2 for medians of 15% and 30%, respectively, of the cortical brain areas in each patient. In multiple regressions, higher body temperature was associated with higher CBF and CDO2 in the early phase. In a similar regression for the vasospasm phase, younger age and longer pulse transit time (lower peripheral resistance) correlated with higher CBF and CDO2, whereas lower hematocrit only correlated with higher CBF but not with CDO2. ICP, CPP, and pressure reactivity index exhibited no independent association with CBF and CDO2. R2 of these regressions were below 0.3. Lower CBF and CDO2 in the early phase correlated with poor outcome, but this only held true for CDO2 in multiple regressions.ConclusionsSystemic and cerebral physiological variables exhibited a modest association with CBF and CDO2. Still, cerebral hypoperfusion and low CDO2 were common and low CDO2 was associated with poor outcome. Xe-CT imaging could be useful to help detect secondary brain injury not evident by high ICP and low CPP.

Accounting for arterial and capillary blood gases for calculation of cerebral blood flow in preterm infants

One of the most feared neurological complications of premature birth is intraventricular hemorrhage, frequently triggered by fluctuations in cerebral blood flow (CBF). Although several techniques for CBF measurement have been developed, they are not part of clinical routine in neonatal intensive care. A promising tool for monitoring of CBF is its numerical assessment using standard clinical parameters such as mean arterial pressure, carbon dioxide partial pressure (pCO2) and oxygen partial pressure (pO2). A standard blood gas analysis is performed on arterial blood. In neonates, capillary blood is widely used for analysis of blood gas parameters. The purpose of this study was the assessment of differences between arterial and capillary analysis of blood gases and adjustment of the mathematical model for CBF calculation to capillary values. The statistical analysis of pCO2 and pO2 values collected from 254 preterm infants with a gestational age of 23–30 weeks revealed no significant differences between arterial and capillary pCO2 and significantly lower values for capillary pO2. The estimated mean differences between arterial and capillary pO2 of 15.15 mmHg (2.02 kPa) resulted in a significantly higher CBF calculated for capillary pO2 compared to CBF calculated for arterial pO2. Two methods for correction of capillary pO2 were proposed and compared, one based on the mean difference and another one based on a regression model.Conclusion: Capillary blood gas analysis with correction for pO2 as proposed in the present work is an acceptable alternative to arterial sampling for the assessment of CBF.What is Known:• Arterial blood analysis is the gold standard in clinical practice. However, capillary blood is widely used for estimating blood gas parameters.• There is no significant difference between the arterial and capillary pCO2values, but the capillary pO2differs significantly from the arterial one.What is New:• The lower capillary pO2values yield significantly higher values of calculated CBF compared to CBF computed from arterial pO2measurements.• Two correction methods for the adjustment of capillary pO2 to arterial pO2that made the difference in the calculated CBF insignificant have been proposed.

Contribution of Inflammation and Hypoperfusion to White Matter Hyperintensities-Related Cognitive Impairment.

White matter hyperintensities (WMHs) of presumed vascular origin are one of the most important neuroimaging markers of cerebral small vessel disease (CSVD), which are closely associated with cognitive impairment. The aim of this study was to elucidate the pathogenesis of WMHs from the perspective of inflammation and hypoperfusion mechanisms. A total of 65 patients with WMHs and 65 healthy controls were enrolled in this study. Inflammatory markers measurements [hypersensitive C-reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2)], cognitive evaluation, and pseudocontinuous arterial spin labeling (PCASL) MRI scanning were performed in all the subjects. The multivariate logistic regression analysis showed that Lp-PLA2 was an independent risk factor for WMHs. Cerebral blood flow (CBF) in the whole brain, gray matter (GM), white matter (WM), left orbital medial frontal gyrus [MFG.L (orbital part)], left middle temporal gyrus (MTG.L), and right thalamus (Tha.R) in the patients was lower than those in the controls and CBF in the left triangular inferior frontal gyrus [IFG.L (triangular part)] was higher in the patients than in the controls. There was a significant correlation between Lp-PLA2 levels and CBF in the whole brain (R = −0.417, p < 0.001) and GM (R = −0.278, p = 0.025), but not in the WM in the patients. Moreover, CBF in the MFG.L (orbital part) and the Tha.R was, respectively, negatively associated with the trail making test (TMT) and the Stroop color word test (SCWT), suggesting the higher CBF, the better executive function. The CBF in the IFG.L (triangular part) was negatively correlated with attention scores in the Cambridge Cognitive Examination-Chinese Version (CAMCOG-C) subitems (R = −0.288, p = 0.020). Our results revealed the vascular inflammation roles in WMHs, which may through the regulation of CBF in the whole brain and GM. Additionally, CBF changes in different brain regions may imply a potential role in the modulation of cognitive function in different domains.

High Resolution Cerebral Blood Flow Simulation and Clinical Verification with a Parallel Domain Decomposition Method

High Resolution Cerebral Blood Flow Simulation and Clinical Verification with a Parallel Domain Decomposition Method

Sleep efficiency is associated with amyloid burden, cerebral blood flow, and cognition in healthy older adults

AbstractBackgroundPrior work has identified associations between sleep quality and amyloid‐beta (Aβ). However, how sleep efficiency relates to Aβ, cerebral blood flow (CBF), and cognition are not well understood. The objective of this study was to evaluate these relationships and the modifying role of APOE4 status.MethodObjective sleep efficiency, Aβ, CBF, and cognitive performance on neuropsychological assessments (MoCA, Flanker, CVLT, and Complex Figure) were examined in a sample of 52 non‐demented, older adults (age=66.5+6.82, 67% female, 27% APOE4 carriers). Sleep efficiency, defined as the percentage of time asleep within a given sleep period, was objectively measured using the GENEActiv tri‐axis accelerometer for an average of 30.25 days. Aβ was measured in vivo using positron emission tomography and the F‐18 florbetaben tracer to calculate composite SUVR scores. Global gray matter CBF was quantified using a pseudo‐continuous arterial spin labeling MRI scan. All analyses were adjusted for age, sex, and education (for cognitive measures).ResultOverall, higher sleep efficiency was associated with lower Aβ burden (p=.04), higher CBF (p=.03), higher MoCA scores (p=.05) and a trend for better Complex Figure Test recall (p=.07). There was a significant moderating effect of APOE4 status on the association between sleep and Aβ, such that poorer sleep efficiency was associated with higher Aβ burden in APOE4 carriers only (p=.01). APOE4 moderation was not observed for CBF. When stratified by high and low sleep efficiency levels (median split), APOE4 carrier status predicted Aβ burden only in individuals with low sleep efficiency (p =.02). Additionally, sleep efficiency predicted performance on long delay free recall of the CVLT and Complex Figure Test (p=.01) in the low sleep efficiency group only. No association between sleep efficiency and Flanker were observed.ConclusionThese results provide evidence that sleep efficiency is associated with brain health and cognition, and suggest a modifying effect of APOE4 on the relationship between sleep and amyloid. Mechanistic evidence from animal models and human studies suggests that impaired slow wave activity during NREM sleep may disrupt dynamic fluid oscillations important for amyloid clearance and brain blood flow. Future work is needed to understand the causal and temporal relationships between these processes.